This application aims to provide Dr. Ana Krieger with the tools needed for an academic career development as a clinician investigator in the field of sleep apnea and vascular dysfunction. Dr. Krieger has been working in this field for the past 3 years and as part of this award, she will complete formal research training under the mentorship and guidance of senior investigators. The long-term goal for her academic career is to utilize the acquired research and mentoring skills to develop her projects as a successful independent investigator in her chosen field of sleep apnea and vasculopathy. The institutional environment at New York University School of Medicine is highly supportive of Dr. Krieger's career development and fully committed to her retention, and will provide a structured research training program through a collaborative effort among several NYU schools, with hands-on experience in research methods, statistics, clinical trials and ethical aspects of human research. Sleep apnea is a prevalent condition shown to be an independent risk factor for stroke. This research proposal will investigate mechanisms of endothelial cell dysfunction associated with thromboregulation in subjects with sleep apnea. The specific hypotheses are that sleep apnea leads to altered ecto-nucleotidase activity in lymphocytes and increased levels of circulating endothelial cells. The specific aims of this research are to: 1) Define the relationship between sleep apnea and NTPDase activity in lymphocytes. The enzyme activity will be correlated with a) the severity of sleep apnea and b) the severity of intermittent hypoxemia;2) Define the relationship between sleep apnea and circulating levels of endothelial cells. The quantification of endothelial cells will be correlated with measurements of sleep apnea as above;3) Characterize the measurable changes in NTPDase activity and circulating endothelial cells after effective treatment of sleep apnea and intermittent hypoxemia. Dr. Krieger will be mentored by experts with complimentary expertise in the field. Due to the severity of vascular outcomes linked to sleep apnea, the elucidation of the underlying dysfunction is a prerequisite to the development of therapeutic protocols capable of attenuating the disease process. Dr. Krieger has the stamina and determination needed from a young investigator to succeed in her area of research interest. Her dedication to the elaboration and funding of this project attests to her potential as a successful clinician scientist in academic medicine.